反応 #53474

反応方程式

pyrrolidine

pyrrolidine

1-{(R*)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

sodium iodide

pyrrolidine

→

3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

溶媒

dichloromethane

反応条件

後処理

1. 1
   workup.STIRRINGstirred for 8 hours
2. 2
   workup.STIRRINGthe mixture is stirred for 20 hours at 20° C
3. 3
   洗浄The reaction mixture is washed with water
4. 4
   乾燥the organic phase is dried over magnesium sulfate
5. 5
   濃縮concentrated to dryness under vacuum (2.7 kPa)
6. 6
   その他The residue obtained
7. 7
   その他is chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 1.2 cm, height 30 cm), at an argon pressure of 0.1 bar
8. 8
   洗浄eluting with dichloromethane
9. 9
   その他with a dichloromethane and methanol mixture (97.5/2.5 by volume) and collecting 3 cm3 fractions
10. 10
    濃縮concentrated to dryness under reduced pressure (2.7 kPa)

実験手順

50 mm3 of pyrrolidine are added to a solution of 0.32 g of 1-{(R*)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form A isomer, and 5 mg of sodium iodide in 10 cm3 of dichloromethane. After stirring for 20 hours at 20° C., 50 mm3 of pyrrolidine are added to the mixture, stirred for 8 hours and then 50 mm3 of pyrrolidine are again added and the mixture is stirred for 20 hours at 20° C. The reaction mixture is washed with water and then the organic phase is dried over magnesium sulfate and concentrated to dryness under vacuum (2.7 kPa). The residue obtained is chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 1.2 cm, height 30 cm), at an argon pressure of 0.1 bar, eluting with dichloromethane and then with a dichloromethane and methanol mixture (97.5/2.5 by volume) and collecting 3 cm3 fractions. Fractions 12 to 40 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.18 g of 1-{(R*)-(4-chlorophenyl)[4-pyrrolidinylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form A isomer, is obtained in the form of a white foam [a]20365 nm=−22.5°+/−0.7 (c=0.5%; dichloromethane) [1H NMR spectrum (300 MHz, CDCl3, δ in ppm): 1.78 (mt, 4H), 2.51 (mt, 4H), 2.81 (s, 3H), 3.58 (s, 2H), 3.84 (mt, 2H), 4.33 (mt, 2H), 4.50 (s, 1H), 6.84 (tt, J=9 and 2.5 Hz, 1H), 6.98 (mt, 2H), from 7.20 to 7.40 (mt, 8H)].

出典